Duodenum-jejunum gastric bypass surgery in diabetic mice results in changes in gut microbiota, improved metabolism, and diabetes remission, according to a new report in The American Journal of Pathology

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Philadelphia, PA, July 11, 2016

Studies have shown that bariatric surgery can lead to remission of type 2 diabetes mellitus (T2DM) in rodents and humans, but this beneficial effect cannot be explained solely by weight loss. In a new study published in The American Journal of Pathology, researchers investigating gastric bypass in a mouse model of T2DM confirmed that bypass surgery improves glucose tolerance and insulin sensitivity. Interestingly, the improved metabolism occurred in conjunction with changes in gut microorganisms, suggesting a potential role for gut microbiota in diabetes remission.

“Our research showed that duodenum-jejunum gastric bypass (DJB) surgery may be applied to cure diabetes of both genetic (mutation) and environmental (diet-induced) origin,” explained lead investigator Xiang Gao, PhD, of State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute and the Collaborative Innovation Center of Genetics and Development, Nanjing University. “We found that DJB surgery induced gut microbiota alterations, which may be the key reason for diabetes remission after bariatric surgery. Our data indicate that suppressed inflammation is the result, not the cause, of diabetes reversal in these genetically modified mice.”

The research was performed in the T2DM mouse model that mimics key symptoms including insulin resistance, high blood levels of lipids, metabolic inflammation, and obesity. These mice harbor genetic mutation in brain-derived neurotrophic factor (Bdnf) leading to Bdnf deficiency. Bdnf is a member of the neurotrophic family of growth factors and is a key regulator of both brain function and metabolic balance.

“Our findings suggest that Bdnf deficiency–induced diabetes can be reversed by DJB surgery in mice, which has potential for the treatment of diabetes in humans,” stated Dr. Gao. He and his team found that bypass surgery reversed the metabolic abnormalities indicative of diabetes without changing Bdnf expression directly. Glucose tolerance and insulin sensitivity were greatly improved and there was less fat accumulation in liver and white adipose tissue. Insulin sensitivity reached normal levels within two weeks following surgery and lasted for at least eight weeks. Six weeks after bypass surgery, oral glucose tolerance in the treated mice was significantly lower than in the diabetic mice that had undergone a sham operation and was similar to levels observed in untreated controls.

Examination of the composition of bacteria and other microorganisms in the gut of mutated mice before and after bypass surgery and in the control group, showed a decrease in pathogenic bacteria and an increase in beneficial microflora that coincided with the onset of better glycemic control. “More mechanistic studies of gut microbiota alterations after bypass surgery are needed to explain how different families of microbiota may regulate nutrient metabolism in the host,” noted Dr. Gao.

Inflammation, especially in white fat tissue and liver, is thought to play an important role in obesity and T2DM. Eight weeks after bypass surgery, significant reductions in inflammatory indicators occurred in the liver and fat tissue, although the post-surgical anti-inflammatory effects occurred after insulin sensitivity improved. “These results indicate that the alleviation of inflammation was not the direct cause of the improvement in insulin sensitivity that resulted from bypass surgery,” commented Dr. Gao.

Copies of this paper are available to credentialed journalists upon request; please contact Eileen Leahy at +1 732 238 3628 or ajpmedia@elsevier.com. Journalists wishing to interview the authors should contact Zhaoyu Lin at linzy@nju.edu.cn.

This research was supported by the Ministry of Science and Technology of China, National Natural Science Foundation of China, and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China.

About The American Journal of PathologyThe American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.

The leading global forum for reporting quality original research on cellular and molecular mechanisms of disease, The American Journal of Pathology is the most highly cited journal in Pathology – close to 40,000 cites in 2015 – with an Impact Factor of 4.206 and Eigenfactor of 0.05638 according to the 2015 Journal Citation Reports®, Thomson Reuters, 2016, and an h-index of 228 according to the 2015 SCImago Journal and Country Rank.

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